Chapter 36: Recognizing Delirium, Dementia, and Depression Manjula Kurella Tamura Division of Nephrology, Stanford University School of Medicine, Palo Alto, California Neuropsychiatric disorders such as delirium, demen- high risk. Several ESKD-specific syndromes of delir- tia, and depression are common yet poorly recognized ium deserve special mention: causes of morbidity and mortality among elderly per- sons with chronic kidney disease (CKD) including Uremic Encephalopathy. end-stage kidney disease (ESKD). Patients with neu- Uremic encephalopathy is a syndrome of delirium ropsychiatric disorders are at higher risk for death, seen in untreated ESKD. It is characterized by lethargy hospitalization, and dialysis withdrawal. These disor- and confusion in early stages and may progress to sei- ders are also likely to reduce quality of life and hinder zures and/or coma. It may be accompanied by other adherence with the complex dietary and medication neurologic signs, such as tremor, myoclonus, or as- regimens prescribed to patients with CKD. This chap- terixis. Although rarely used for diagnostic purposes, ter will review the evaluation and management of de- the EEG shows a characteristic pattern in patients with lirium, dementia, and depression among persons with uremic encephalopathy.2 The syndrome is rapidly re- CKD and ESKD. versed with dialysis or kidney transplantation. Dialysis Dysequilibrium. DELIRIUM This syndrome of delirium is seen during or after the first several dialysis treatments. It is most likely Delirium is an acute confusional state characterized to occur in elderly patients with severe azotemia by a recent onset of fluctuating awareness, impair- undergoing high efficiency hemodialysis; however, ment of memory and attention, and disorganized it has also been reported in patients undergoing thinking that can be attributable to a medical con- peritoneal dialysis and long-term hemodialysis.3 dition, intoxication, or medication side effects. A The syndrome is characterized by symptoms of diagnostic algorithm based on Diagnostic and Sta- headache, visual disturbance, nausea, or agitation, tistical Manual of Mental Disorders, fourth edition and in severe cases, delirium, lethargy, seizures, and (DSM-IV) criteria, the Confusion Assessment even coma. The incidence and severity of this syn- Method, has a sensitivity and specificity for delir- drome are felt to be declining because of earlier ini- ium detection Ͼ90% (Table 1).1 tiation of dialysis and institution of preventative measures in high-risk patients (Table 2). Risk Factors Delirium is typically precipitated by an acute or Prevention and Management of Delirium subacute event such as a neurologic disorder In hospitalized patients, preventative measures can (stroke, subdural hematoma, hypertensive encepha- reduce incidence and costs associated with delirium 4 lopathy), infection, electrolyte disorder (hypoglyce- (Table 3). Once identified, management of delirium mia, hyponatremia, hypernatremia, hypercalcemia), is aimed at identification and treatment of precipitat- intoxication (alcohol, drugs, star fruit), or sleep disor- ing factors and management of behavioral symptoms. der. Elderly patients with cognitive or sensory impair- Pharmacologic therapy is indicated only when delir- ment or those taking multiple medications are thought to be most vulnerable for delirium. Typically, Correspondence: Manjula Kurella Tamura, Division of Nephrol- one or more precipitants exist in a vulnerable patient. ogy, Stanford University School of Medicine, 780 Welch Road, Elderly patients with multiple chronic diseases, such Suite 106, Palo Alto, CA 94304. E-mail: [email protected] as elderly patients with ESKD, are thus at especially Copyright ᮊ 2009 by the American Society of Nephrology American Society of Nephrology Geriatric Nephrology Curriculum 1 Table 1. Confusion assessment method 60% to 80% of cases of dementia, vascu- Criteria Assessment lar dementia for 10% to 20%, and other 1. Acute onset and fluctuating course Is there an acute change in mental status from baseline? syndromes such as Parkinson’s disease– Does mental status fluctuate throughout the day? associated dementia and frontotempo- 2. Inattention Is there difficulty focusing attention? ral dementia for the remainder. In the 3. Disorganized thinking Is thinking disorganized or incoherent? ESKD population, some studies suggest 4. Altered level of consciousness Is there hyperalertness, lethargy, stupor, or coma? that vascular dementia may be much Diagnosis requires criteria 1, 2, and either 3 or 4. more prominent than in the general Adapted from Inouye et al.1 population.6,7 However, it should be ium threatens patient safety or interrupts essential therapy. In noted that the distinction between vas- these cases, haloperidol is the agent of choice, with a usual starting cular dementia and Alzheimer’s dementia is not always dose of 0.25 to 0.5 mg twice daily. No dosage adjustment is needed straightforward, because there is considerable overlap in risk in ESKD. Atypical antipsychotic medications, such as risperidone, factors and clinical features. Dialysis dementia is a syndrome olanzapine, and quietapine, have also been used for this purpose. related to aluminum intoxication first described several de- Because of a possible risk of increased mortality when used in cades ago when aluminum contamination of dialysate fluid patients with dementia, short-term use is recommended.5 Benzo- and the use of aluminum containing binders were more prev- diazepines, atypical antipsychotics, and some antidepressants alent; however, this disorder is now felt to be rare. have also been used for treatment of delirium, but these agents have side effects that make them less desirable as first-line agents Risk Factors except in the case of benzodiazepines for alcohol withdrawal. Sup- Older age is a strong risk factor for dementia and mild cognitive portive care to prevent aspiration, deep venous thrombosis, and impairment. The prevalence of dementia quadruples with each pressure sores should also be provided in all patients. decade of age above the age of 60, reaching 30% over the age of 85.8 Stroke and vascular risk factors associated with increased stroke risk, such as hypertension, hyperlipidemia, and diabetes, DEMENTIA are linked with an increased risk for dementia in most studies. Anemia, a nontraditional vascular risk factor, has also been linked Dementia is a chronic confusional state characterized by im- with dementia and cognitive impairment in both the general el- 9,10 pairment in memory and at least one other cognitive domain, derly population and among hemodialysis patients. such as language, orientation, reasoning, or executive func- There is growing recognition that CKD is also a strong risk tioning. The impairment in cognitive function must represent factor for dementia and mild cognitive impairment, indepen- a decline from the patient’s baseline level of cognitive function dent of age and traditional vascular risk factors. The prevalence and must be severe enough to interfere with daily activities and of cognitive impairment seems to rise early in the course of independence. The term mild cognitive impairment denotes CKD, and increases as GFR declines, reaching 20% for persons Ͻ 2 11 cognitive impairment (usually memory impairment) beyond with a GFR 20 ml/min per 1.73 m (Figure 1). Among that associated with normal aging but without associated func- hemodialysis patients, the prevalence of cognitive impairment 12,13 tional impairments. Individuals with mild cognitive impair- is even higher, estimated at 27% to 37%. An issue that re- ment have a high risk of progression to dementia. mains unresolved is the extent to which neurodegenerative dis- ease, subclinical cerebrovascular disease, unresolved uremia, Epidemiology or the dialysis process itself contributes to cognitive impair- In the general population, Alzheimer’s dementia accounts for ment and dementia. Evaluation History taking (ideally from the patient and caregiver) should focus on the duration and severity of cognitive and behavioral deficits, as well as use of medications that might interfere with cognitive function such as antihistamines, antipsychotics, and Table 2. Prevention of dialysis dysequilibrium 1. Identify high-risk patient: elderly, severe azotemia, initial dialysis treatment 2. Perform reduced efficiency dialysis: reduce blood and dialysate flow rates or perform continuous renal replacement therapy Figure 1. Unadjusted prevalence of cognitive impairment and 3. Increase dialysate sodium concentration cerebrovascular disease by estimated GFR among 23,405 US 4. Administer mannitol adults. Adapted from reference 11. Adapted from Owen et al.24 2 Geriatric Nephrology Curriculum American Society of Nephrology Table 3. Measures for prevention of delirium in also be ruled out. The role of testing for genetic markers of hospitalized patients dementia risk (e.g., apoE variants) is controversial. 1. Provide orienting communication 2. Use adaptive equipment such as visual and/or hearing aids Management 3. Encourage early mobilization Two classes of medications are now available for treatment of 4. Prevent dehydration both Alzheimer’s and vascular dementia. Cholinesterase in- 5. Provide uninterrupted sleep time hibitors are approved for treatment of mild to moderate de- 6. Avoid psychoactive drugs mentia, whereas memantine, an N-methyl-D-aspartate recep- 7. Treat pain tor antagonist, is approved for treatment of moderate to severe Alzheimer’s dementia and